title: Glycolaldehyde induces cytotoxicity and increases glutathione and multidrug-resistance-associated protein levels in Schwann cells.
abstract: Schwann cell injury is observed in diabetic neuropathy. It is speculated that glycolaldehyde (GA), a precursor of advanced glycation end products (AGEs), contributes to the pathogenesis and development of diabetic neuropathy. Here, we demonstrated for the first time that GA at near-physiological concentration decreased the viability of rat Schwann cells. In contrast, methylglyoxal, glyoxal, and 3-deoxyglucosone, all of which are AGE precursors, had no effects on cell viability. It is well known that methylglyoxal causes oxidative damage. In the present study, however, GA failed to induce reactive oxygen species production in Schwann cells. The addition of glutathione (GSH) or N-acetyl-L-cysteine protected Schwann cells from the loss of viability induced by GA. Moreover, GA increased intracellular GSH level and γ-glutamylcysteine synthetase mRNA level. Flow cytometric analysis revealed that GA increased multidrug-resistance-associated protein 1 (MRP1) level as well. Moreover, we demonstrated that the knockdown of MRP1 with small interfering RNA (siRNA) enhanced the loss of cell viability induced by GA. Taken together, these findings suggest that MRP1, together with GSH, plays an important role in the GA-induced toxicity in Schwann cells.
authors.affiliation: Hokkaido Pharmaceutical University School of Pharmacy, Hokkaido 047–0264, Japan.
authors.forename: Keisuke
authors.initials: K
authors.lastname: Sato
authors.forename: Ryosuke
authors.initials: R
authors.lastname: Tatsunami
authors.forename: Kaori
authors.initials: K
authors.lastname: Yama
authors.forename: Yoshiko
authors.initials: Y
authors.lastname: Tampo
mesh_terms: D000079:Acetaldehyde / Q000031:analogs & derivatives* / Q000633:toxicity; D000111:Acetylcysteine / Q000494:pharmacology; D000818:Animals; D002470:Cell Survival / Q000187:drug effects; D005434:Flow Cytometry; D005978:Glutathione / Q000378:metabolism*; D027425:ATP-Binding Cassette, Sub-Family C Proteins / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D034741:RNA, Small Interfering / Q000235:genetics; D051381:Rats; D017382:Reactive Oxygen Species / Q000378:metabolism; D012583:Schwann Cells / Q000187:drug effects* / Q000378:metabolism
chemical_list: D000079:Acetaldehyde; D000111:Acetylcysteine; D005978:Glutathione; D027425:ATP-Binding Cassette, Sub-Family C Proteins; D034741:RNA, Small Interfering; D017382:Reactive Oxygen Species; C010972:glycolaldehyde; C421109:multidrug resistance-associated protein 1